The human cytochrome P450 (CYP) metabolizes more than 100 structurally diverse exogenous and endogenous molecules. The CYP3A5 is a major P450 enzyme in the liver and represents 50% of the total hepatic CYP3A content in people expressing CYP3A5. The single nucleotide polymorphisms in CYP3A5*3 and CYP3A5*6 that resulted in the absence of CYP3A5 from tissues were noted in some people. Polymorphisms of potential relevance to leukemia and myelodysplastic syndrome (MDS) have been described for various CYP. The bone marrow and/or peripheral blood from 188 acute myeloid leukemia (AML) patients, 101 chronic myeloid leukemia (CML), 40 MDS, and 270 normal controls were analyzed by a PCR-RFLP assay to evaluate the association of the CYP3A5 polymorphisms with myeloid leukemia. Our data showed that 15/188 (8%), 8/101 (7.9%), and 3/40 (7.5%) of the patients (i.e., 188 AML, 101 CML, 40 MDS) were CYP3A5*1/*1; 88/188 (46.8%), 47/101 (46.5%), and 20/40 (50%) were CYP3A5*1/*3; and 85/188 (45.2%), 46/101 (45.5%), and 17/40 (42.5%) carried the CYP3A5*3/*3 genotype, respectively. CYP3A5*6 was not found in any of the patients' specimens. Similar frequencies of CYP3A5*3 were observed in the leukemic patients and normal controls. Consequently, the finding suggests that the CYP3A5 polymorphism was not associated with the risk of myeloid leukemia.